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J. Schlom



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    OA18 - New Insights in the Treatment of Thymic Malignancies (ID 408)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      OA18.03 - Safety and Clinical Activity of Avelumab (MSB0010718C; Anti-PD-L1) in Patients with Advanced Thymic Epithelial Tumors (TETs) (ID 6141)

      11:20 - 11:30  |  Author(s): J. Schlom

      • Abstract
      • Slides

      Background:
      Avelumab (MSB0010718C) is a fully human, IgG1 anti-PD-L1 antibody under clinical development. We report safety and clinical activity in patients with relapsed TETs enrolled in a phase I trial (NCT01772004).

      Methods:
      Patients previously treated with one or more standard therapies, no prior immune checkpoint inhibitors, and with no history of autoimmune disease were eligible. Treatment consisted of avelumab at doses of 10-20 mg/kg iv q2 weeks until disease progression or toxicity. Responses were assessed q6 weeks by RECIST 1.1. Correlative studies included evaluation of tumor cell PD-L1 expression and peripheral blood immune subset analysis.

      Results:
      7 patients with thymoma and 1 with thymic carcinoma (TC) were treated with avelumab; 3 patients with thymoma (2 B3, 1 B2/B3) received avelumab 20 mg/kg; 4 patients with thymoma (1 B1, 3 B2) and 1 TC received 10 mg/kg. Two (29%) patients with thymoma had a confirmed partial response (PR;1 at 20 mg/kg, and 1 at 10 mg/kg), 2 (29%) had unconfirmed PRs, 2 (29%) stable disease (SD) and 1 (14%) progressive disease; the TC patient had SD. Most adverse events (AEs) were mild (grade 1 or 2). Grade 3 and 4 AEs were observed in 3 (38%) patients each, and included potential immune-related AEs (irAEs) in 5 cases. irAEs resolved completely with oral steroids in 3 patients, and incompletely in 1 patient. One patient required cyclosporine A for treatment of irAEs. All 4 responders experienced irAEs (myositis in 3 patients, all after 1 dose of avelumab, and enteritis in 1 patient). Pre- and post-treatment tumor biopsies were available for analysis of PD-L1 expression and intratumoral immune infiltrates from three patients treated at 20 mg/kg. In one case the post-treatment biopsy showed necrotic tissue with no viable tumor. In the other two cases diffuse, membranous PD-L1 staining of epithelial cells was seen in both pre- and post-treatment biopsies. The immune infiltrate consisted of immature T cells in pre-treatment tumor samples in both cases. The post-treatment biopsy showed continued presence of immature T cells in one case and a mature CD8+ T cell phenotype in the other case. Decreased CTLA4+ regulatory T cells and decreased ratio of granulocytic vs. monocytic myeloid-derived suppressor cells was seen post-treatment at the 20mg/kg dose.

      Conclusion:
      Avelumab is active in patients with recurrent thymoma. Strategies need to be developed to reduce the risk of development of irAEs in response to immune checkpoint inhibitor therapy in patients with thymoma.

      Information from this presentation has been removed upon request of the author.

      Information from this presentation has been removed upon request of the author.